1. Field of the Invention
The invention concerns compositions and methods for formulating and delivering cosmeceutical skin preparations. The disclosed compositions are particularly adapted for delivery of acidic agents for skin renewal and treatment agents.
2. Description of Related Art
Human skin acts as a protective barrier to both physical and chemical insults. The properties of the cutaneous layer are important to the cosmetic industry in developing effective and safe skin preparations in addition to medical concerns in treating damage to the skin surface in conditions such as acne.
The epidermal surface is acidic and has been the subject of studies on epidermal permeability and formation. The chemistry and function of dry skin and moisturizers has been extensively reviewed (Loden and Howard, eds, 2000) in the context of understanding the factors involved in developing skin moisturizers and protective formulations.
Skin homeostasis normally is maintained at about pH 5 allowing lipid barrier repairs. At more neutral or alkaline pH, skin repair is inhibited (Mauro, 1998). Studies have shown that there are racial differences in the stratum corneum pH gradient at least with respect to the surface layers. Significant differences between Caucasian and black African-American skin was reported by Berasdesca, et al. (1998), although no differences were found in the deeper stratum corneum layers.
Mauro et al. states that the skin's lipid barrier is impeded at neutral pH, independent of ionic effects. Epidermal permeability barrier homeostasis requires the post-secretory processing of polar lipid precursors into nonpolar lipid products within the stratum corneum (SC) interstices by a family of lipid hydrolase enzymes. A specific requirement for beta-glucocerebrosidase (beta-GlcCer'ase), which exhibits a distinct optimum acidic pH, is particularly well documented. The investigators sought to determine whether the recovery of the barrier after acute insults requires acidification of the SC. They examined permeability barrier recovery by assessing changes in transepidermal water loss (TEWL), SC membrane ultrastructure utilizing ruthenium tetroxide (Ru04) postfixation, and beta-GlcCer'ase activity by in situ zymography at an acidic vs. neutral pH. Barrier recovery proceeded normally when acetone-treated skin was exposed to solutions buffered to an acidic pH. In contrast, the initiation of barrier recovery was slowed when treated skin was exposed to neutral or alkaline pH, regardless of buffer composition. In addition, enhancement of the alkaline buffer-induced delay in barrier recovery occurred with Ca2+ and K+ inclusion in the buffer. Moreover, the pH-dependent alteration in barrier recovery appeared to occur through a mechanism that was independent of Ca2+ or K+ controlled lamellar body secretion, since both the formation and secretion of lamellar bodies proceeded comparably at pH 5.5 and pH 7.4. Exposure to pH 7.4 (but not pH 5.5) resulted in both the persistence of immature, extracellular lamellar membrane structures, and a marked decrease in the in situ activity of beta-GlcCer'ase. These results suggest first that an acidic extracellular pH is necessary for the initiation of barrier recovery, and second that the delay in barrier recovery is a consequence of inhibition of post-secretory lipid processing.
Kligman (2000) states “. . . our concept of humectants (as moisturizers) falls short of explaining how they work. It is worth repeating that used alone they are not much good. It is only when they are properly formulated with other ingredients that their potential benefits are realized. Other factors such as pH also have to be taken into account, because proteases which lead to orderly desquamation of horny cells within the stratum corneum are activated only at acid pHs of 4 to 5. Also the various hydrolytic enzymes, which are found in the stratum corneum and which are essential to the formation of the intercorneocyte lipids that establish the impermeability of the barrier, are activated only at acid pHs” (Kligman, 2000).
Feingold and Elias (2000) state that the epidermal surface has been known for many years to be acidic, but the role of this acidic pH of the stratum corneum in barrier homeostasis was unknown. It is well recognized that β-glucocerebrosidase is most active at pH 5.5. Recently, we have examined barrier recovery of an acidic vs. neutral pH. Barrier recovery proceeded normally when acetone treated skin was exposed to solutions buffered to an acidic pH. In contrast, barrier recovery was delayed when treated skin was exposed to neutral or alkaline pH regardless of buffer composition” (in Dermatology, eds. Loden and Maibach, 2000). These results indicate that an acidic extracellular pH in the SC is required for normal extracellular lipid processing and normal barrier homeostasis.
The majority of marketed skin treatment preparations use emulsifying agents that are non-volatile and accordingly remain on the skin until removed by cleansing. Most facial care cosmetics are formulated with about 5–7% emulsifying agents, at a pH of 6.5–8.0 to insure product stability, and contain on average about 75% water. After application to the skin the water used in the formulation evaporates off the skin quickly, leaving up to approximately a 20% concentration of emulsifying agents on the skin. This high level of emulsifying agent is capable of emulsifying the natural lipids in the skin which can be removed on cleansing the skin. The net result is detrimental to the skin for two reasons: the residual pH of 6.5 to 8.0 is not favorable for the repair of the skin's lipid barrier layer and the residual high level of emulsifying agents is conducive to removal of the natural lipids in the skin leading to an even drier skin condition. The stress of the emulsifying agent residue causes overstimulation of the skin, increased oil production, irritation and blemishes. Stronger emulsions are difficult to neutralize for older skin and sensitive skin. Harsh emulsifiers may actually damage skin by dissolving the skin's protective lipid barrier, which is essential to healthy looking skin. Additionally, perspiration may remove the active ingredients deposited on the skin.